Objective: To study the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.
Methods: The effects of DHA on the proliferation of acute myeloid leukemia cells and the inhibitory effect of Z-VAD-FMK on the DHA-induced cell apoptosis were detected by CCK-8 assay. The expression level of cleaved-caspased 3 was detected by indirect immunofluorescence. Western blot was used to quantify the protein expression of PTEN, p-Akt, AKT, β-actin, and the apoptosis-associated proteins, such as C-PARP, Cleaved-caspase3 and Caspase3 respectively.
Results: DHA induced the AML cell apoptosis with concentration-dependent manner (rKasumi-1=-0.959, rKG-1=-0.956). The DHA could induce the accumulation of cleaved-caspase 3 and C-PARP in AML cells, activate PTEN gene and inhibited Akt phosphorylation. Apoptosis inhibitor Z-VAD-FMK could partially restored the activity of DHA-inhibited cell proliferation.
Conclusion: Dihydroartemisinin induces AML cell apoptosis by inhibition of PTEN/AKT pathway. Dihydroartemisinin is expected to be a safe and effective drug for treatment of acute myeloid leukemia.
题目: 双氢青蒿素抑制PTEN/AKT通路诱导急性髓系白血病细胞凋亡.
目的: 研究双氢青蒿素对人急性髓系白血病细胞增殖抑制及凋亡的诱导作用.
方法: 采用CCK-8试剂盒检测细胞增殖抑制率及Z-VAD-FMK抑制DHA诱导细胞凋亡的作用；用间接免疫荧光技术检测细胞内Cleaved-caspase3的表达；应用Western blot检测细胞凋亡相关蛋白C-PARP、Cleaved-caspase3、Caspase3及PTEN、p-Akt、AKT、β-Actin蛋白的表达.
结果: DHA呈剂量依赖性诱导急性髓系白血病细胞的凋亡（rKasumi-1=-0.959，rKG-1= -0.956）。DHA能诱导急性髓系白血病细胞内Cleaved-caspase3和C-PARP的累积。激活PTEN基因，抑制Akt蛋白磷酸化。凋亡抑制剂Z-VAD-FMK可部分恢复DHA抑制细胞增殖的活性.
结论: 双氢青蒿素抑制PTEN/AKT通路诱导急性髓系白血病细胞凋亡。双氢青蒿素有望成为安全有效的治疗急性髓系白血病药物.